The purpose of this study is to develop metabolic strategies for studying central catecholamine metabolism in man and to carry out pharmacokinetic studies of psychoactive drugs. A radioisotope strategy employing C14-dopamine injected intravenously has been developed to assess central nervous system norepinephrine metabolism. An intravenous probenecid test has been developed to assess relative synthesis rates of dopamine and serotonin. The kinetics of probenecid in the circulation and the time course of its distribution in the central nervous system have been studied after a 40 mg/kg infusion. Stable isotope strategies for studying brain amine metabolism have been explored. Methionine, labelled with a deuterated methyl group, can be infused intravenously to label methylated catecholamine metabolites. Quantitative synthesis rates for dopamine in rat brain have been calculated using this technique. Deuterated homovanillic acid, the major metabolite of dopamine, disappears from the circulation with a half life of approximately one hour and can be accounted for quantitatively in the urine.